title: SPG4 gene promoter regulation via Elk1 transcription factor.
abstract: The most common cause of autosomal dominant hereditary spastic paraplegia, that is characterized with axonal degeneration in corticospinal tracts and posterior columns, is known to be caused by mutations in the SPG4 gene which encodes spastin, a microtubule severing ATPase belonging to AAA family. Spastin promotes the formation of microtubule networks that are essential for axon growth and branching which are important for neuronal plasticity. Mutations observed in SPG4 gene of hereditary spastic paraplegia patients have been shown to cause reduced spastin levels. In addition to mutations, transcriptional regulation of spastin gene expression may also affect spastin level. ETS (E Twenty Six-specific)-domain transcription factor, Elk1, has been shown to be important for synaptic plasticity and interact with microtubules. In this study, we aimed to identify the critical promoter regions of SPG4 gene and effects of Elk on SPG4 gene expression. We identified 700 bp TATA-less promoter including a critical CpG island as an optimal promoter, and deletion of the CpG island gradually decreased the SPG4 promoter activity. In addition, we identified the binding sites of Elk1 on the SPG4 promoter by EMSA. Over-expression of Elk1 showed that it repressed the SPG4 promoter and also decreased spastin protein level in SHSY-5Y cells.
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Canbaz
authors.forename: Koray
authors.initials: K
authors.lastname: Kırımtay
authors.forename: Esra
authors.initials: E
authors.lastname: Karaca
authors.forename: Arzu
authors.initials: A
authors.lastname: Karabay
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D019295:Computational Biology; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000074181:Spastin; D014162:Transfection; D050807:ets-Domain Protein Elk-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D017931:DNA Primers; C494113:Elk1 protein, mouse; D050807:ets-Domain Protein Elk-1; D004247:DNA; D008156:Luciferases; D000251:Adenosine Triphosphatases; D000074181:Spastin; C498515:Spast protein, mouse